Elucidation of molecular mechanism that controls the maintenance of retinal stem cells

视网膜边缘区域含有持续增殖的视网膜干细胞，并在很长一段时间内保持未分化状态。我们之前已经发现信号分子Wnt2b作为维持视网膜干细胞未分化状态的视网膜干细胞因子。在本研究项目中，我们研究了Wnt信号的下游通路，重点研究了转录因子。我们发现Wnt激活包括c-myc在内的多种转录因子，这些转录因子反过来协同激活转录抑制因子c-hairy1。我们还发现c-hairy1的激活反过来是抑制视网膜干细胞分化的必要和充分的。因此，c-hairy1作为Wnt信号下游的一个节点来维持视网膜干细胞。

The marginal region of the retina contains retinal stem cells that continue to proliferate and remain undifferentiated for a long period. We have previously identified a signaling molecule Wnt2b as a retinal stem cell factor that maintains undifferentiated state of the retinal stem cells. In this research project, we investigated downstream pathway of the Wnt signaling, especially focusing on transcription factors. We have found that Wnt activates multiple transcription factors including c-myc, which in turn cooperatively activate a transcriptional repressor c-hairy1. We have also revealed that the activation of c-hairy1 in turn was necessary and sufficient to inhibit differentiation of the retinal stem cells. Thus, c-hairy1 functions as a node downstream of Wnt signaling to maintain the retinal stem cells.